1. Field of the Invention
The present invention pertains to the monitoring and measurement of glucose transport and metabolism in tissues and organs after the administration of non-radioisotope-labeled glucose or glucose analog to a subject, and in particular, to methods and systems for quantitatively measuring glucose transport and metabolism by chemical-exchange-sensitive spin-locking magnetic resonance and to using these measurements to monitor the onset, progression or treatment efficacy in any diseases or disorders with altered glucose transport and/or metabolism.
2. Description of the Related Art
Because glucose fuels cellular function, glucose transport and, metabolism are sensitive biomarkers of cellular dysfunction in afflictions such as cancer, stroke, Alzheimer's and psychiatric diseases. Direct detection of glucose transport in vivo has been established in human and animal studies by 13C and 1H NMR spectroscopy, but low glucose concentrations severely limit sensitivity1-4. Clinical positron emission tomography (PET) scans with radioisotope-labeled deoxyglucose detect altered metabolism, but radiation exposure limits scan frequency and excludes certain patient groups. Additionally, this procedure is expensive and has low spatial and temporal resolutions.
Many key biomolecules (including glucose) can be indirectly detected via their chemical exchange (CE) with water. One magnetic resonance imaging (MRI) approach to detect levels of glucose uses the chemical exchange saturation transfer (CEST) technique. In the “glucoCEST” MRI method, low-power, long-duration (several seconds) radiofrequency (RF) irradiation at the resonance frequency of the labile hydroxyl protons in glucose provide a non-invasive magnetic label that is transferred to water protons by CE. This saturation transfer attenuates the bulk water signal, improving the detectability to labile glucose protons. However, glucoCEST MRI faces two major technical challenges, namely, the relatively low sensitivity and difficulty in quantification. In particular, previous studies suggest tissue glucose concentration changes must be ˜5-10 mM as a threshold for detection at a magnetic field strength of 9.4 Tesla. Furthermore, the CEST signal is strongly affected by other relaxation effects such as transverse relaxation time (T1), spin-spin relaxation time (T2) and magnetization transfer, and lacks a reliable means to quantify glucose concentration.
Thus, there is a need for an alternative magnetic resonance (MR) method and system to quantify and non-invasively measure glucose transport and metabolism with higher sensitivity to detect and monitor the onset and progression of various disorders and diseases. The increased sensitivity is desirable for assessment in clinical environments.